Document Detail

Paraoxonase-1 Q192R polymorphism is not associated with clopidogrel response in Chinese stroke patients.
MedLine Citation:
PMID:  23346768     Owner:  NLM     Status:  In-Process    
It is well known that CYP2C19*2/*2 is associated with attenuated response to clopidogrel, but recent findings indicated that in white patients, paraoxonase-1 (PON1) 192Q/Q was a major determinant of clopidogrel efficacy. The objective of this research was to assess the impact of PON1 Q192R polymorphism on the maximum platelet aggregation (MPA) and the anti-platelet effect of clopidogrel in clopidogrel-treated Chinese stroke patients. The study recruited 183 eligible Chinese stroke patients treated with a loading dose of 300-mg clopidogrel and a 75-mg daily maintenance dose. CYP2C19*2 and PON1 Q192R were genotyped, a subcohort of 13 patients with CYP2C19 *2/*2 genotype was excluded. Finally 170 patients with CYP2C19*1/*1 (wild-type homozygotes, n = 87) or CYP2C19*1/*2 (mutant heterozygotes, n = 83) were enrolled in the study population. These patients were divided into three groups according to their PON1 Q192R genotype: wild-type homozygotes, PON1 192QQ, n = 17; mutant heterozygotes, PON1 192QR, n = 81; mutant homozygotes, PON1 192RR, n = 72. MPA was measured by light transmittance aggregometry (LTA) to assess platelet function after seven 75-mg maintenance doses of clopidogrel before discharge. In those patients who were carriers of 1 mutant allele (PON1 Q/R192), ADP-induced MPA were not significantly different compared with wild-type homozygous patients [30.5% (IQR, 17.5 to 49.1%) versus 25.0% (IQR, 10.0 to 52.5%), respectively; P = 0.910]. In addition, in the patients who were carriers of the 2 mutant allele (PON1 R/R192), MPA were also not significantly different from wild-type homozygous patients [29.2% (IQR, 15.0 to 43.4%) versus 25.0% (IQR, 10.0 to 52.5%), respectively; P = 0.717]. Results of a multivariable linear regression model demonstrated that PON1 192R allele carriage was not independently associated with ADP-induced MPA measurements (P = 0.408). PON1 Q192R polymorphism does not seem to exhibit any impact on MPA and clopidogrel response at all.
Jie Yang; Jun-Shan Zhou; Jie Tan; Bang-Shun He; Jian-Jun Zou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Die Pharmazie     Volume:  67     ISSN:  0031-7144     ISO Abbreviation:  Pharmazie     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2013-01-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9800766     Medline TA:  Pharmazie     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1026-9     Citation Subset:  IM    
Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
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